The oral immunomodulatory drug lenalidomide is active and may provide prolonged responses in certain patients with a rare and aggressive subtype of primary cutaneous lymphoma, according to results of a phase 2 study.

In the study, which comprised 19 patients with primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT), 5 patients (26.3%) had a response at 6 months, and there were still 3 patients in response at 12 months. The findings were reported in the Journal of Investigative Dermatology.

In an exploratory analysis, reducing the dose of lenalidomide was associated with prolonged response and improved survival, noted lead author Marie Beylot-Barry, MD, of the dermatology department, Hôpital Saint-André, CHU Bordeaux, France, and her colleagues.

“Lenalidomide at reduced doses may allow prolonged responses in few patients, and represents a therapeutic option in relapsing/refractory PCDLBCL, LT,” the researchers wrote.

Found mostly on the lower limbs of elderly patients, PCDLBCL, LT exhibits aggressive behavior and is associated with a high rate of skin recurrences. First-line therapy for the cutaneous lymphoma is typically rituximab and chemotherapy, regardless of clinical stage or patient age, the researchers wrote, though primary resistance or recurrence after treatment occurs in about half of patients. “In such relapsing or refractory cases, no treatment has demonstrated a sustained benefit thus far,” they noted.

Lenalidomide has already demonstrated efficacy in relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and it induces inhibition of cell signaling, engaging NF-kappaB signaling. PCDLBCL, LT is marked by genetic alterations leading to the NF-kappaB pathway, which represents a therapeutic target.

Dr. Beylot-Barry and her colleagues initiated a multicenter, single-arm, phase 2 trial of 19 patients refractory/relapsing PCDLBCL, LT. Median progression-free survival in the trial was 4.9 months. The 6-month overall response rate – the primary endpoint of the trial – was 26.3%, which was not significantly superior to a prespecified 20% minimal response rate, according to the researchers.

“However, it was a stringent goal, and other secondary evaluations have to be considered in this context, such as a 6-month disease control rate at 42%,” they wrote.

Reduced doses were associated with improved outcomes, they added. Comparing the nine patients who had lenalidomide dose reductions to those who did not, there was a higher likelihood of 6- to 11-month overall response rate (44.4% vs. 10.0%; P = .11) and lower risk of disease progression or death (hazard ratio, 0.54; 95% confidence interval, 0.19-1.59; P = .27).

Grade 3 adverse events were primarily hematologic, and two deaths occurred (pulmonary embolism and sepsis).

Taken together, the encouraging results at reduced doses, the advanced age of the patients, and the high rate of adverse events suggests a role for lenalidomide as a part of combination treatment for PCDLBCL, LT in future trials, the researchers concluded.

The study was supported by grants from the French Ministry of Health and Celgene. The researchers reported having no financial disclosures.

SOURCE: Beylot-Barry M et al. J Invest Dermatol. 2018 Mar 26. doi: 10.1016/j.jid.2018.03.1516.

Lenalidomide yields responses in a rare cutaneous lymphoma